PCT Published Patent Application No. WO 2006/110917, PCT Published Patent Application No. WO 2010/045251, PCT Published Patent Application No. WO 2010/045197, PCT Published Patent Application No. WO 2011/047174, PCT Published Patent Application No. WO 2011/002708, PCT Published Patent Application No. WO 2011/106729 and PCT Published Patent Application No. WO 2013/154712, discloses certain spiro-oxindole compounds, methods of preparing the spiro-oxindole compounds, pharmaceutical compositions comprising the spiro-oxindole compounds and/or methods of using the spiro-oxindole compounds.
One of these spiro-oxindole compounds is funapide, which is also known as TV-45070 or XEN402. Funapide has the following formula (I-S):
and has the chemical name of (S)-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one.
In particular, PCT Published Patent Application No. WO 2011/002708 specifically discloses funapide and its corresponding (R)-enantiomer; PCT Published Patent Application No. WO 2011/047174 discloses methods of preparing funapide by resolving its racemate by either SMB chromatography or by chiral HPLC; and PCT Published Patent Application No. WO 2013/154712 discloses methods of preparing funapide by asymmetric synthesis.
Funapide is the (S)-enantiomer of the racemic compound previously disclosed in PCT Published Patent Application No. WO 2006/110917 as compound #428 therein. Compound #428 is also known as XEN401.
Funapide and pharmaceutical compositions comprising funapide are useful for the treatment of sodium channel-mediated diseases, preferably diseases related to pain, central nervous conditions such as epilepsy, anxiety, depression and bipolar disease; cardiovascular conditions such as arrhythmias, atrial fibrillation and ventricular fibrillation; neuromuscular conditions such as restless leg syndrome; neuroprotection against stroke, neural trauma and multiple sclerosis; and channelopathies such as erythromelalgia and familial rectal pain syndrome.
The relevant disclosures of the above published patent applications are incorporated in full by reference herein.
Polymorphism, the occurrence of different crystalline forms of the same molecule, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties such as melting point, thermal behaviors (e.g., measured by differential scanning calorimetry—“DSC” or thermogravimetric analysis—“TGA”), X-ray diffraction pattern, infrared absorption fingerprint, and solid state (13C—) NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Different solid state forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different solid state forms and solvates may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, changing the dissolution profile in a favorable direction, or improving stability (polymorphic as well as chemical stability) and shelf-life. These variations in the properties of different solid state forms may also offer improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different solid state forms and solvates of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess variations in the properties and characteristics of a solid active pharmaceutical ingredient.
Discovering new solid state forms and solvates of a pharmaceutical product may yield materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New solid state forms of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity or polymorphic stability which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life (chemical/physical stability). For at least these reasons, there is a need for solid state forms (including solvated forms) of funapide.